U.S. Patent Publication No. 2006/0229297 discloses (thio)-carbamoyl-cyclohexane derivatives that are D3 and D2 dopamine receptor subtype preferring ligands, having the formula (I):
wherein R1, R2, X, and n are as defined therein.
One particular compound disclosed in the Hungarian patent application No. P0700339 is trans-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine hydrochloride, which is also known as trans-1{4-[2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethyl-urea hydrochloride, the structural formula for which is shown below:

Trans-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine hydrochloride is an orally active and very potent dopamine D3/D2 receptor antagonist, which binds with significantly higher potency to D3 than D2 receptors. The D3 receptor antagonism is about one order of magnitude greater than the D2 receptor antagonism, which is believed to counteract some of the extrapyramidal side effects produced by D2 receptor antagonists. Another unique feature of trans-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine hydrochloride is that in vivo it acts as a “dopamine system stabilizer.” In this regard, it has preferential dopaminergic actions in the limbic regions and displays both (partial) agonist and antagonist activity on biosynthesis (and release) modulating presynaptic D2 receptors depending on the functional status of the particular dopaminergic system.
These compounds have high or very high affinity for dopamine D3 receptors and moderate to high affinity to dopamine D2 receptors always in such a combination that the D3 affinity is 5 to 200 fold higher than the D2 affinity. In addition, the compounds have even higher selectivity over other receptors, such as alpha-1 receptors. The dual (i.e. D3 and D2) receptor functional antagonism coupled in the above mentioned particular proportion is especially important as it allows the simultaneous manifestation of the beneficial effects of modulation of both the D3 and D2 receptors, however, without the appearance of the known disadvantages of each individual receptor action.
In addition to the increased relative affinity to dopamine D3 to D2, trans-4-{2-[4-(2,3-dichlorophenyl)-piperazin-1-yl]ethyl}-N,N-dimethylcarbamoyl-cyclohexylamine hydrochloride has a low potency at other receptor sites such as the 5-HT2C, histamine H1, and adrenergic receptor sites, which suggest a lower potential for side effects such as extrapyramidal symptoms (EPS) and body weight gain.
These compounds are useful in the treatment and/or prevention of pathological conditions which require the modulation of dopamine receptors.